Tissue engineering using autologous, allogeneic, or xenogeneic cells in combination with biocompatible materials provides one of the more promising treatments for tissue loss or end-stage organ failure. Cell transplantation faces many challenges however, including providing an adequate cell source, immunoprotection of the transplanted cells, creation of a vascular bed to support and maintain long-term cell survival, and biocompatibility (both in vitro and in vivo) of the material substrate for the delivery of the cells.
In order for a biomaterial to be successfully integrated in vivo for the creation of new tissue, the ability of a substrate to support cellular attachment, promote the growth and differentiation of stroma and parenchymal cells, induce a minimal inflammatory response, and be biodegradable could be useful. Thus, the development of scalable processes to create three-dimensional patterning on materials are needed that will allow for the selective integration of different cell adhesion peptides to possibly permit selective adhesion of various cells to specific areas of the material. Such spatial organization to guide the development of the tissues in an organized fashion might be achieved by micropatterning of proteins on the substrates.
Micropatterning a biomaterial into microscale or nanoscale features to provide topographical cues for cell alignment may also be needed for engineering nerve cells to direct the axons to their intended location. Thus, micropatterned grooves can play a role in directing the extending axon projection to the area of intended innervation. Extracellular voltage gradients are a normal environmental component in the developing nervous system, thus electroactive (electrically conductive) biomaterials, including biodegradable materials, may also play a role in the formation and regeneration of nerve cells.
One approach to micropatterning is conventional lithography that has been widely used in the semiconductor industry. In conventional lithography, organic solvents are normally utilized to dissolve the photoresist in order to form the desired pattern (See, for example: Moreau, W. M. Semiconductor Lithography: Principles, Practices, and Materials, Plenum, New York, 1987, which is incorporated herein by reference in its entirety). However, such a process can lead to the denaturation of biomolecules and cells. What is needed are new photoresist materials and methods that are biocompatible. If possible, desirable bio-photoresist, or “bioresist”, materials, could be used in a conventional lithographic process without using organic solvents or harsh bases for development of the patterned image, yet still allow sub-micron to nanometer scale patterning.